NMDA receptor activation induces differential epigenetic modification of Bdnf promoters in hippocampal neurons.
NMDA receptor activation induces differential epigenetic modification of Bdnf promoters in hippocampal neurons.
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DOI：
10.1007/s00726-009-0315-y
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发表时间：
2010-04
期刊：
影响因子：
3.5
通讯作者：
Lipsky, Robert H.
中科院分区：
文献类型：
--
作者：
Tian, Feng;Marini, Ann M.;Lipsky, Robert H.
关键词：
脑源性神经营养因子（brain-derived neurotrophic factor，BDNF）基因的转录调控已被广泛研究。然而，对染色质修饰机制的理解，对控制转录至关重要的事件，是基本的。我们专注于两个激活依赖区域的BDNF基因物理连接到已知的转录位点外显子1和4。使用染色质免疫沉淀（ChIP）测定，我们确定，N-甲基-D-天冬氨酸（NMDA）受体激活去抑制启动子1和4介导的转录。这种去抑制与组蛋白去乙酰化酶1（HDAC 1）和甲基胞嘧啶结合蛋白2（MeCP 2）的每个启动子区域附近的已知的转录起始位点在培养的海马神经元的占用率降低。这些变化并没有发生在转录起始上游的所有位点。总之，这些发现表明，组蛋白和其他DNA结合蛋白参与重塑染色质在一些，但不是所有的网站，在BDNF启动子1和4，并与NMDA受体依赖性增加转录。
Transcriptional regulation of the gene encoding brain-derived neurotrophic factor (BDNF) has been widely studied. However, an understanding of mechanisms modifying chromatin, events that are essential for controlling transcription, is rudimentary. We focused on two activation dependent regions of the Bdnf gene physically linked to known transcription sites for exons 1 and 4. Using chromatin immunoprecipitation (ChIP) assays, we determined that N-methyl-D-aspartate (NMDA) receptor activation derepressed promoters 1 and 4-mediated transcription. This derepression correlated with reduced occupancy by histone deacetylase 1 (HDAC1) and methyl cytosine binding protein 2 (MeCP2) of each promoter region near known transcription start sites in cultured hippocampal neurons. These changes did not occur at all sites upstream of transcription initiation. Taken together, these findings suggest that histone and other DNA binding proteins are involved in remodeling of chromatin at some, but not all sites, within Bdnf promoters 1 and 4 and are associated with NMDA receptor-dependent increases in transcription.
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影响因子：
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10.1002/ajmg.b.30109
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